This Phase I SBIR application is presented by Bistech, Inc. of Woburn, MA. It will test the feasibility of using a new inhaled pharmaceutical agent, pneumoreductive surfactant (PRS), to treat pulmonary emphysema, a progressive and disabling disease that affects millions of individuals throughout the world. Existing medical therapies for emphysema, such as bronchodilators and anti-inflammatory drugs, are of limited benefit since they do not address the fundamental physiological defect in this disease: loss of elastic recoil caused by destruction of the collagen and elastin fibers of the lung. Two factors determine lung elastic recoil: 1) stretching of the tissue fiber network and 2) surface tension generated by the surface film at the alveolar air-liquid interface. In, theory, elastic recoil could be restored in emphysema either by repairing the tissue fiber network or by increasing surface tension. While medical therapies cannot readily accomplish the former, they may be able to accomplish the latter. Prototype formulations of pneumoreductive surfactant have been developed by Bistech. In preliminary in vitro testing and short term in vivo testing, these formulations appear to increase recoil effectively and safely. The studies proposed here will extend these preliminary observations, and examine whether PRS can be developed for clinical testing. The specific aim of this proposal is to evaluate short and long term physiological and biological responses to PRS administration in an experimental model of emphysema that accurately represents the disease as it presents in humans. The studies are designed to provide detailed information about the effects of PRS on lung function in vivo, and to identify any potential toxic effects of prolonged PRS exposure. If Phase I proves successful, a Phase II application will be filed to complete preclinical animal testing and product formulation, initiate pharmacology-toxicology studies, develop a manufacturing plan, and begin the planning of a Phase 1 clinical trial in human patients.